4-67738448-TAAA-TAA

Variant names:

• chr4-67738448-TA-T
• rs766610755
• NM_000406.3:c.*2031delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000406.3(GNRHR):​c.*2031delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 143,416 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0039 (3 hom., cov: 32)
• Consequence: GNRHR NM_000406.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 0 publications found

Genes affected

GNRHR (HGNC:4421): (gonadotropin releasing hormone receptor) This gene encodes the receptor for type 1 gonadotropin-releasing hormone. This receptor is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate. Following binding of gonadotropin-releasing hormone, the receptor associates with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Activation of the receptor ultimately causes the release of gonadotropic luteinizing hormone (LH) and follicle stimulating hormone (FSH). Defects in this gene are a cause of hypogonadotropic hypogonadism (HH). Alternative splicing results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for this gene. [provided by RefSeq, Jul 2008]

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000406.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRHR	NM_000406.3	MANE Select	c.*2031delT		3_prime_UTR	Exon 3 of 3	NP_000397.1	P30968-1
	GNRHR	NM_001012763.2		c.*2140delT		3_prime_UTR	Exon 3 of 3	NP_001012781.1	P30968-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRHR	ENST00000226413.5	TSL:1 MANE Select	c.*2031delT		3_prime_UTR	Exon 3 of 3	ENSP00000226413.5	P30968-1
	UBA6-DT	ENST00000500538.7	TSL:1	n.1920+6115delA		intron	N/A
	UBA6-DT	ENST00000502758.1	TSL:4	n.202+6115delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 556 AN: 143366 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00384

Gnomad ASJ AF: 0.00929

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00219

Gnomad FIN AF: 0.00683

Gnomad MID AF: 0.0323

Gnomad NFE AF: 0.00529

Gnomad OTH AF: 0.00561

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00389 AC: 558 AN: 143416 Hom.: 3 Cov.: 32 AF XY: 0.00362 AC XY: 252 AN XY: 69584

African (AFR) AF: 0.000914 AC: 36 AN: 39394

American (AMR) AF: 0.00390 AC: 56 AN: 14342

Ashkenazi Jewish (ASJ) AF: 0.00929 AC: 31 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00219 AC: 10 AN: 4558

European-Finnish (FIN) AF: 0.00683 AC: 59 AN: 8636

Middle Eastern (MID) AF: 0.0352 AC: 10 AN: 284

European-Non Finnish (NFE) AF: 0.00530 AC: 344 AN: 64962

Other (OTH) AF: 0.00607 AC: 12 AN: 1978

Alfa AF: 0.00130 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766610755; hg19: chr4-68604166; COSMIC: COSV56933279;